[1]刘泽世a,殷 鉴a,雷 静a,等.磷霉素联合多黏菌素B 对碳青霉烯类耐药肠杆菌目细菌的体外抗菌活性分析[J].现代检验医学杂志,2023,38(04):163-168.[doi:10.3969/j.issn.1671-7414.2023.04.030]
　LIU Zeshia,YIN Jiana,LEI Jinga,et al.In Vitro Antibacterial Activity Analysis of Fosfomycin Combined with Polymyxin B Against Carbapenem Resistant Enterobacterales[J].Journal of Modern Laboratory Medicine,2023,38(04):163-168.[doi:10.3969/j.issn.1671-7414.2023.04.030]
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磷霉素联合多黏菌素B 对碳青霉烯类耐药肠杆菌目细菌的体外抗菌活性分析()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年04期
页码:
163-168
栏目:
研究简报·实验技术
出版日期:
2023-07-15

文章信息/Info

Title:
In Vitro Antibacterial Activity Analysis of Fosfomycin Combined with Polymyxin B Against Carbapenem Resistant Enterobacterales
文章编号:
1671-7414（2023）04-163-06
作者:
刘泽世a; 殷 鉴a; 雷 静a; 张 雪a; 张彦平a; 耿 燕a; 蔡 艳b
（西安交通大学第二附属医院a. 检验科；b. 药学部，西安 710004）
Author(s):
LIU Zeshia;  YIN Jiana;  LEI Jinga;  ZHANG Xuea;  ZHANG Yanpinga;  GENG Yana;  CAI Yanb
(a. Department of Medical Laboratory；b. Department of Pharmacy, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004，China)
关键词:
磷霉素; 多黏菌素B; 碳青霉烯类耐药肠杆菌目细菌; 联合药敏; 部分抑菌浓度指数
分类号:
R378.2；R446.5
DOI:
10.3969/j.issn.1671-7414.2023.04.030
文献标志码:
A
摘要:
目的　分析磷霉素联合多黏菌素B 对碳青霉烯类耐药肠杆菌目细菌(carbapenem-resistant Enterobacterales,CRE) 的体外抗菌活性。方法　收集2020 ～ 2022 年西安交通大学第二附属医院分离的CRE 78 株，其中碳青霉烯类耐药大肠埃希菌（carbapenem-resistant Escherichia coli，CREC）32 株、碳青霉烯类耐药肺炎克雷伯菌（carbapenem-resistantKlebsiella pneumonia，CRKP）46 株；碳青霉烯类敏感肠杆菌目细菌(carbapenem-sensitive Enterobacterales, CSE)132 株，其中碳青霉烯类敏感大肠埃希菌（carbapenem-sensitive Escherichia coli，CSEC）72 株、碳青霉烯类敏感肺炎克雷伯菌（carbapenem-sensitive Klebsiella pneumonia，CSKP）60 株。采用琼脂稀释法和肉汤微量稀释法（broth microdilution,BMD）分别测定磷霉素和多黏菌素B 的最低抑菌浓度（minimum inhibitory concentration, MIC），采用肉汤微量稀释棋盘法测定CRE 对磷霉素联合多黏菌素B 的最低抑菌浓度，并计算部分抑菌浓度指数(fractional inhibitory concentrationindex, FIC)，判定其联合效应。结果　78 株CRE 中28 株对磷霉素耐药，总耐药率为35.90%（28/78），其中6 株同时还对多黏菌素B 耐药，总耐药率为7.69%（6/78）。132 株CSE 中18 株仅对磷霉素耐药，总耐药率为13.64%（18/132）；未检测到对多黏菌素B 耐药。多黏菌素B 联合磷霉素对CREC 为相加作用，对CRKP 为协同作用。结论　磷霉素和多黏菌素B 单药耐药率均明显升高，二者联合用药可有效降低耐药率，提供一种新的治疗思路。
Abstract:
Objective　To analyze the in vitro antibacterial activity of fosfomycin combined with polymyxin B against carbapenem resistant Enterobacterales (CRE). Methods　78 strains of CRE isolated from the Second Affiliated Hospital of Xi’an Jiaotong University from 2020 to 2022 were collected, including 32 strains of carbapenem-resistant Escherichia coli (CREC), and 46 strains of carbapenem-resistant Klebsiella pneumonia(CRKP), 132 strains of carbapenem-sensitive Enterobacterales(CSE), including 72 strains of carbapenem-sensitive Escherichia coli (CSEC), and 60 strains carbapenemsensitive Klebsiella pneumonia (CSKP). The minimum inhibitory concentration (MIC) of fosfomycin and polymyxin B was determined by AGAR dilution method, and minimum inhibitory concentration（BMD）, and the MIC of fosfomycin combined with polymyxin B was determined by broth microdilution chessboard method. Fractional inhibitory concentration index (FIC) was calculated to determine the joint effect. Results　In this study, 28 of 78 CRE strains were resistant to fosfomycin, with a total resistance rate of 35.90% (28/78), of which 6 were also resistant to polymyxin B, and the total resistance rate was 7.69% (6/78). 18 of 132 CSE strains were only resistant to fosfomycin, with the total resistance rate of 13.64% (18/132). No resistance to polymyxin B was detected. Polymyxin B combined with fosfomycin has additive effect on CREC and synergistic effect on CRKP. Conclusion　The single drug resistance rate of fosfomycin and polymyxin B increased significantly, the combination of fosfomycin and polymyxin B can effectively reduce the drug resistance rate and provide a new treatment idea.

参考文献/References:

[1] STEWARDSON A J, MARIMUTHU K, SENGUPTA S, et al. Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study[J]. Lancet Infectious Diseases, 2019, 19(6): 601-610.
[2] HU Fupin, GUO Yan, YANG Yang, et al. Resistance reported from China antimicrobial surveillance network (CHINET) in 2018 [J]. European Journal of Clinical Microbiology & Infectious Diseases, 2019, 38(12):2275-2281.
[3] VAN DUIN D, DOI Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae[J]. Virulence, 2017, 8(4): 460-469.
[4] LI Chen, LI Yi, ZHAO Zhichang, et al. Treatment options and clinical outcomes for carbapenem-resistant Enterobacteriaceae bloodstream infection in a Chinese university hospital[J]. Journal of Infection and Public Health, 2019, 12(1): 26-31.
[5] ZHANG Yawei, WANG Qi, YIN Yuyao, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae infections: report from the China CRE network [J]. Antimicrob Agents Chemother, 2018, 62(2): e01882-17.
[6] 梅清, 耿士窠, 房晓伟, 等．头孢他啶- 阿维巴坦联合多黏菌素E 对广泛耐药铜绿假单胞菌的体外抗菌活性[J]．中华危重病急救医学, 2019, 31(10)：1212-1218． MEI Qing, GENG Shike, FANG Xiaowei, et al. In vitro activity of ceftazidime-avibactam combined with colistin against extensively drug-resistant Pseudomonas aeruginosa [J]. Chinese Critical Care Medicine, 2019, 31(10): 1212-1218.
[7] 林琳, 肖晓光, 王楠, 等．阿维巴坦联合头孢他啶或氨曲南对耐碳青霉烯肠杆菌科细菌体外抗菌活性研究[J]．中华医院感染学杂志, 2020, 30(1): 15-19. LIN Lin, XIAO Xiaoguang, WANG Nan, et al. In vitro antimicrobial activities of ceftazidime-avibactam or aztreonam-avibactam against carbapenemresistant Enterobacteriaceae[J]. Chinese Journal of Nosocomiology, 2020, 30(1): 15-19.
[8] 更藏达杰, 张斌．住院患者血流感染革兰阴性菌分布特征和耐药性及耐药菌株碳青霉烯酶基因检测[J]. 中国病原生物学杂志, 2020, 15(9): 1107-1110. GENG CANG Dajie, ZHANG Bin. Distribution characteristics, drug resistance, and prevalence of carbapenem genes in gram-negative bacteria in patients with a bloodstream infection[J]. Journal of Pathogen Biology, 2020, 15(9): 1107-1110.
[9] EL-WAFA W M A, IBRAHIM Y M. In vitro activity of fosfomycin in double and triple combinations with imipenem, ciprofloxacin and tobramycin against multidrug-resistant Escherichia coli[J]. Current Microbiology, 2020, 77(5): 755-761.
[10] 王妍, 郭晓芳, 陈显成, 等．多黏菌素B 为基础联合治疗泛耐药菌重症肺炎的临床观察[J]. 中国感染控制杂志, 2020, 19(11): 976-980. WANG Yan, GUO Xiaofang, CHEN Xiancheng, et al. Clinical observation on polymyxin B-based combination therapy for severe pneumonia caused by extensively drug-resistant bacteria [J]. Chinese Journal of Infection Control, 2020, 19(11): 976-980.
[11] Clinical and Laboratory Standards Institute. Performa nce standards for antimicrobial susceptibility testing. Thirty-two informational supplement [S]. Wayne：PA, CLSI supplement M100S, 2022.
[12] 汪复, 张婴元．实用抗感染治疗学[M]．3 版．北京：人民卫生出版社, 2020． WANG Fu, ZHANG Yingyuan, et al. Practical antiinfective therapeutics [M]. 3rd Ed. Beijing: People’s Medical Publishing House,2020.
[13] SATLIN M J, CHEN Liang, PATEL G, et al. Multicenter clinical and molecular epidemiological analysis of bacteremia due to carbapenem-resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States[J]. Antimicrobial Agents and Chemotherapy, 2017, 61(4): e02349-16.
[14] TACCONELLI E, CARRARA E, SAVOLDI A, et al. Discovery, research, and development of new antibiotics:the WHO priority list of antibiotic-resistant bacteria and tuberculosis[J]. Lancet Infectious Diseases, 2018, 18(3): 318-327.
[15] ZHANG Ya w e i , WANG Qi, YIN Yuyao, e t al. Epidemiology of carbapenem-resi s t a n t Enterobacteriaceae infections: report from the China CRE Network [J]. Antimicrobial Agents and Chemotherapy, 2018, 62(2): e01882-17.
[16] BROLUND A, LAGERQVIST N, BYFORS S, et al. Worsening epidemiological situation of carbapenemaseproducing Enterobacteriaceae in Europe, assessment by national experts from 37 countries, July 2018 [J]. Euro Surveill 2019, 24(9)：1900123.
[17] 肖晓, 杭修兵, 王梦, 等．耐碳青霉烯类肠杆菌目细菌耐药性、临床感染特征及mcr 基因分析[J]. 中国感染控制杂志, 2023, 22(1): 31-37. XIAO Xiao, HANG Xiubing, WANG Meng, et al. Antimicrobial resistance, clinical infection characteristics and mcr genes of carbapenem-resistant Enterobacterales[J]. Chinese Journal of Infection Control, 2023, 22(1): 31-37.
[18] 史静, 陈晴毅, 徐绣宇, 等．碳青霉烯耐药肠杆菌科细菌感染脓毒症患者的危险因素和耐药性[J]. 中华医院感染学杂志, 2022, 32(23): 3547-3551. SHI Jing, CHEN Qingyi, XU Xiuyu, et al. Analysis of risk factors and drug resistance of carbapenem-resistant Enterobacteria in patients with sepsis[J]. Chinese Journal of Nosocomiology, 2022, 32(23): 3547-3551.
[19] TSAI W C, SYUE L S, KO W C, et al. Antimicrobial treatment of monomicrobial phenotypic carbapenemresistant Klebsiella pneumoniae bacteremia: Two are better than one[J]. Journal of Microbiology, Immunology, and Infection, 2022, 55(6): 1219-1228.
[20] 丁丽, 陈佰义, 李敏, 等．碳青霉烯类耐药革兰阴性菌联合药敏试验及报告专家共识[J]. 中国感染与化疗杂志, 2023, 23(1): 80-90． DING Li, CHEN Baiyi, LI Min, et al. Expert consensus on antimicrobial synergy testing and reporting of carbapenem-resistant Gram-negative bacteria[J]. Chinese Journal of Infection and Chemotherapy, 2023, 23(1): 80-90.
[21] WEERAKOON D, PETROV K, KHALID S. How does polymyxin B1 enter the outer membrane of E. coli? [J]. Biophysical Journal, 2022,121(Issue 3, Supplement 1):161a.
[22] AL-MARZOOQ F, GHAZAWI A, TARIQ S, et al. Discerning the role of polymyxin B nonapeptide in restoring the antibacterial activity of azithromycin against antibiotic-resistant Escherichia coli [J]. Front Microbiol, 2022, 13: 998671.
[23] 沈芳, 全晶晶, 刘炉香, 等．碳青霉烯耐药肠杆菌目细菌耐药性及耐药传播机制研究[J]. 中华微生物学和免疫学杂志, 2021, 41(9): 679-686. SHEN Fang, QUAN Jingjing, LIU Luxiang, et al. Resistance and transmission mechanisms of carbapenem-resistant Enterobacterales[J]. Chinese Journal of Microbiology and Immunology, 2021, 41(9):679-686.
[24] 黄加铭, 王启, 徐玉金, 等．2015~2020 年某院CRE分布、耐药性及碳青霉烯酶基因检测结果分析[J]．检验医学与临床, 2023, 20(4): 490-494. HUANG Jiaming, WANG Qi, XU Yujin, et al. Analysis of CRE distribution, drug resistance and carbapenemase gene detection results in a hospital from 2015 to 2020[J]. Laboratory Medicine and Clinic, 2023, 20(4):490-494.
[25] D?EZ-AGUILAR M, CANT?N R. New microbiological aspects of fosfomycin[J]. Revista Espanola de Quimioterapia, 2019, 32 (Suppl 1): 8-18.
[26] 王立新, 苏云福, 王毅．临床病原菌磷霉素耐药机制研究进展[J]．检验医学, 2022, 37(10): 993-997. WANG Lixin, SU Yunfu, WANG Yi. Research progress on the drug resistance mechanism of clinical pathogens to fosfomycin[J]. Laboratory Medicine, 2022, 37(10):993-997.
[27] FALAGAS M E, GIANNOPOULOU K P, KOKOLAKIS G N, et al. Fosfomycin: use beyond urinary tract and gastrointestinal infections[J]. Clinical Infectious Diseases, 2008, 46(7): 1069-1077.
[28] FALAGAS M E, KASTORIS A C, KARAGEORGOPOULOS D E, et al. Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gramnegative bacilli: a systematic review of microbiological, animal and clinical studies[J]. International Journal of Antimicrobial Agents, 2009, 34(2): 111-120.
[29] 麦荣嘉, 马丹娟, 邓文喻, 等．磷霉素、多粘菌素B等抗菌药物对儿童感染NDM-1 肺炎克雷伯菌的体外药敏研究[J]. 现代医院, 2021, 21(4): 636-639. MAI Rongjia, MA Danjuan, DENG Wenyu, et al. Study on vitro susceptibility of fosfomycin and polymyxin B to Klebsiella pneumoniae infected with NDM-1 in children[J]. Modern Hospital, 2021, 21(4): 636-639.
[30] 贾艳增, 时东彦．替加环素与临床常用抗生素对碳青霉烯耐药高毒力肺炎克雷伯菌体外联合药敏试验[J]．现代检验医学杂志, 2021, 36(3): 113-117. JIA Yanzeng, SHI Dongyan. Tigecycline in combination with commonly used antibiotics against clinical isolates of hypervirulent and carbapenem-resistant Klebsiella pneumoniae in vitro[J]. Journal of Modern Laboratory Medicine, 2021, 36(3): 113-117.

相似文献/References:

[1]刘 周,杭修兵,储雯雯,等.耐碳青霉烯类大肠埃希菌临床分布、耐药特征及携带mcr 基因分析[J].现代检验医学杂志,2022,37(05):1.[doi:10.3969/j.issn.1671-7414.2022.05.001]
　LIU Zhou,HANG Xiu-bing,CHU Wen-wen,et al.Clinical Distribution, Antimicrobial Agent Resistance and mcr Genes Analysis of Carbapenem-resistant Escherichia coli[J].Journal of Modern Laboratory Medicine,2022,37(04):1.[doi:10.3969/j.issn.1671-7414.2022.05.001]

备注/Memo

备注/Memo:
基金项目： 陕西省重点研发计划国际科技合作计划项目（2021KW-65）：基于基因分型和PK/PD 的双碳青酶烯联用治疗CRKP 肺部感染的给药方案优化策略。
作者简介：刘泽世（1986-），男，硕士，主管技师，研究方向：病原生物学检测，E-mial:281026973@qq.com。
通讯作者：蔡艳(1981-)，女，博士研究生，副主任药师，研究方向：抗菌药物合理应用，E-mail：caiyan029@163.com。
更新日期/Last Update: 2023-07-15